Approximately one in 20,000 people in North America and Europe are affected by Huntington's disease (HD), a neurodegenerative disorder. There is no effective treatment for this devastating brain disease. However, since the discovery of the gene that causes HD in 1993, much has been learned about the pathological and molecular mechanisms of this disease using cell and transgenic animal models (mouse, Drosophila, and C. elegans). Current disease models, however, are not ideal for therapeutic drug screening: cultured cells lack the context of the nervous systems and do not reflect the metabolism of drugs in the human body; Drosophila and C. elegans are invertebrates and thus have very different physiology and organ systems from humans; and mice cannot be used for high throughput drug screening. This SBIR aims to generate transgenic zebrafish (Danio rerio) lines for screening therapeutics for HD. This SBIR will characterize embryogenesis, patterning and HD pathology in the transgenic fish lines, and validate their use in drug screening. Zebrafish have multiple advantages for studying neurodegeneration, including transparency that allows easy observation of neurons, and straightforward assessment of neuronal survival in the whole embryo. [unreadable] [unreadable] [unreadable]